The H Factor
Researchers uncover a new connection between elevated FHR-4 levels and AMD
Phoebe Harkin | | Quick Read
Researchers have found increased levels of complement factor H-related Protein 4 (FHR-4) in plasma and serum samples of 484 late AMD patients (characterized by geographic atrophy and/or choroidal neovascularization) compared with 522 phenotype controls (1). Further, the research team – based out of Cardiff University, Queen Mary University of London, the University of Manchester, and Radboud University Medical Center – found FHR-4 present in the AMD-affected parts of the eye.
To discover whether increased levels of FHR-4 were a cause or consequence of AMD, the team turned to genetics. The genes coding for factor H, FHR-4 and other FH-family proteins are typically found in a tight cluster on chromosome 1. A genome-wide association study revealed that variants in this gene cluster have the biggest effect on FHR-4 levels, overlapping with other chromosome 1 variants that determine a well-established 20-year-old genetic risk of AMD. The team’s findings suggest that genetically determined increases in blood FHR-4 levels lead to more FHR-4 in the eye, which in turn increase the risk of the uncontrolled complement activation that drives the disease. The team hopes its findings will provide a new route to treatment by restoring complement control in the eye.
- V Cipriani et al., Nature, 11, 778 (2020). PMID: 32034129.